Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

PURPOSE: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS: Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS: First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION: MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.

Multidisciplinary management of sexual and gender minorities with bladder cancer.

Bladder cancer, a common urologic malignancy, has poor morbidity and mortality in sexual and gender minority (SGM) individuals, stemming from higher risk, poor access to care and lack of quality cancer care. To begin addressing this disparity, this review offers key considerations for evaluation, diagnosis and treatment of SGM individuals with bladder cancer. In addition to thorough medical and surgical history, initial evaluation should include discussion of patient goals for sexual function and organ preservation, as well as an evaluation of sexual function. Prior gender affirming surgery and patient specific sexual function goals will impact diagnosis and treatment approaches, including surgical and radiation therapy. Throughout care for SGM individuals with bladder cancer, it is critical to acknowledge the systemic discrimination that may be experienced by these individuals and approach conversations with sensitivity and humility and incorporate mental and social support as appropriate.

Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation.

Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathologic factors on chemotherapy response, the role of the gut microbiome (GM) in bladder cancer chemotherapy response remains poorly understood. This study examines the variance in the GM of patients with bladder cancer compared with healthy adults, and investigates GM compositional differences between patients who respond to chemotherapy versus those who exhibit residual disease.Our study reveals distinct clustering, effectively separating the bladder cancer and healthy cohorts. However, no significant differences were observed between chemotherapy responders and nonresponders within community subgroups. Machine learning models based on responder status outperformed clinical variables in predicting complete response (AUC 0.88 vs. AUC 0.50), although no single microbial species emerged as a fully reliable biomarker.The evaluation of short chain fatty acid (SCFA) concentration in blood and stool revealed no correlation with responder status. Still, SCFA analysis showed a higher abundance of Akkermansia (rs = 0.51, P = 0.017) and Clostridia (rs = 0.52, P = 0.018), which correlated with increased levels of detectable fecal isobutyric acid. Higher levels of fecal Lactobacillus (rs = 0.49, P = 0.02) and Enterobacteriaceae (rs = 0.52, P < 0.03) correlated with increased fecal propionic acid.In conclusion, our study constitutes the first large-scale, multicenter assessment of GM composition, suggesting the potential for a complex microbial signature to predict patients more likely to respond to NAC based on multiple taxa. SIGNIFICANCE: Our study highlights results that link the composition of the GM to the efficacy of NAC in MIBC. We discovered that patients with higher levels of Bacteroides experienced a worse response to NAC. This microbial signature shows promise as a superior predictor of treatment response over traditional clinical variables. Although preliminary, our findings advocate for larger, more detailed studies to validate these associations.

Population Estimates of Ovarian Cancer Risk in a Cohort of Patients with Bladder Cancer.

BACKGROUND AND OBJECTIVE: The rationale for oophorectomy during female cystectomy is not adequately supported. The co-occurrence and timing of bladder cancer (BC) and ovarian cancer (OC) in females harboring OC germline mutations remain unclear. Our objective was to determine the frequency and temporal occurrence of OC germline variants among females with BC. METHODS: We used genetic and phenotypic data from the UK Biobank (UKB). The study cohort was defined using ICD-10/ICD-9 codes for BC and further stratified to identify 1347 females. Analysis was restricted to variants with high/moderate impact for initial regression. ClinVar was used to interpret pathogenicity. Pathogenic/likely pathogenic (P/LP) variants were assessed by age of presentation, family history, and concomitant malignancies. Statistical analysis was performed using UKB DNAnexus JupyterLab and RStudio. KEY FINDINGS AND LIMITATIONS: Some 3.4% of the patients had at least one of 15 variants for OC. CHEK2 and PALB2 mutations represented the highest ratio of overall/pathogenic variants (15.8% and 6.6%). Although females with P/LP OC mutations had a higher risk of OC, diagnosis of OC preceded BC by 11.3 yr (±12.5 yr) in the group with mutations and by 15.6 yr (±11.3 yr) in the group without mutations. The group with P/LP variants had higher rates of maternal (14.63% vs 8.12%; p = 0.04) and sibling (9.76% vs 3.98%; p = 0.02) breast cancer and of maternal colon cancer (9.76% vs 4.21%), and lower maternal life expectancy (75.34 vs 68.15 yr; p = 0.0014). UKB provides limited staging/treatment history and its exome sequencing platform may miss variants or provide insufficient coverage for genotyping. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study provides evidence against routine oophorectomy for reducing OC risk in females with BC. The results highlight that the development of OC occurred 11 yr before diagnosis of BC for patients with OC mutations and 15 yr before diagnosis of BC for patients without OC mutations. PATIENT SUMMARY: Although removal of the ovaries in women with bladder cancer is common, no studies have shown that this strategy has a benefit. Our study of women diagnosed with bladder cancer who had genetic mutations associated with ovarian cancer shows that their risk of developing ovarian cancer after bladder cancer is low. These findings provide evidence against removal of the ovaries when the bladder is being removed as treatment for bladder cancer.

Current Trends and Challenges of Microbiome Research in Bladder Cancer.

PURPOSE OF THE REVIEW: Microbiome research has provided valuable insights into the associations between microbial communities and bladder cancer. However, this field faces significant challenges that hinder the interpretation, generalization, and translation of findings into clinical practice. This review aims to elucidate these challenges and highlight the importance of addressing them for the advancement of microbiome research in bladder cancer. RECENT FINDINGS: Recent findings underscore the complexities involved in microbiome research, particularly in the context of bladder cancer. Challenges include low microbial biomass in urine samples, potential contamination issues during collection and processing, variability in sequencing methods and primer selection, and the difficulty of establishing causality between microbiota and bladder cancer. Studies have shown the impact of sample storage conditions and DNA isolation kits on microbiome analysis, emphasizing the need for standardization. Additionally, variations in urine collection methods can introduce contamination and affect results. The choice of 16S rRNA gene amplicon sequencing or shotgun metagenomic sequencing introduces technical challenges, including primer selection and sequencing read length. Establishing causality between the microbiota and bladder cancer requires experimental methods like fecal microbiota transplantation and human microbiota-associated murine models, which face their own set of challenges. Translating microbiome research into therapeutic applications is hindered by methodological variability, incomplete understanding of bioactive molecules, imperfect animal models, and the inherent heterogeneity of microbiome communities among individuals. Microbiome research in bladder cancer presents significant challenges stemming from technical and conceptual complexities. Addressing these challenges through standardization, improved experimental models, and advanced analytical approaches is essential for advancing our understanding of the microbiome's role in bladder cancer and its potential clinical applications. Achieving this goal can lead to improved patient outcomes and novel therapeutic strategies in the future.

Novel non-MRI imaging techniques for primary diagnosis of prostate cancer: micro-ultrasound, contrast-enhanced ultrasound, elastography, multiparametric ultrasound, and PSMA PET/CT.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) provides enhanced diagnostic accuracy in the detection of prostate cancer, but is not devoid of limitations. Given the recent evolution of non-MRI imaging techniques, this critical review of the literature aimed at summarizing the available evidence on ultrasound-based and nuclear medicine imaging technologies in the initial diagnosis of PCa. METHODS: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies examining their diagnostic performance in the primary diagnosis of PCa, weighted against a histological confirmation of PCa diagnosis, using a free-text protocol. Retrospective and prospective studies, both comparative and non-comparative, systematic reviews (SR) and meta-analysis (MA) were included. Based on authors' expert opinion, studies were selected, data extracted, and results qualitatively described. RESULTS: Micro-ultrasound (micro-US) appears as an appealing diagnostic strategy given its high accuracy in detection of PCa, apparently non-inferior to mpMRI. The use of multiparametric US (mpUS) likely gives an advantage in terms of effectiveness coming from the combination of different modalities, especially when certain modalities are combined. Prostate-specific membrane antigen (PSMA) PET/CT may represent a whole-body, one-step approach for appropriate diagnosis and staging of PCa. The direct relationship between lesions avidity of radiotracers and histopathologic and prognostic features, and its valid diagnostic performance represents appealing characteristics. However, intrinsic limits of each of these techniques exist and further research is needed before definitively considering them reliable tools for accurate PCa diagnosis. Other novel technologies, such as elastography and multiparametric US, currently relies on a limited number of studies, and therefore evidence about them remains preliminary. CONCLUSION: Evidence on the role of non-MRI imaging options in the primary diagnosis of PCa is steadily building up. This testifies a growing interest towards novel technologies that might allow overcoming some of the limitations of current gold standard MRI imaging.

Female sexual function evaluation and intraoperative vaginal reconstruction in bladder cancer.

RC significantly negatively impacts sexual function (SF) in both men and women. While significant research resources have been allocated to examine the deleterious effects of post prostatectomy erectile dysfunction, little attention has been directed towards female sexual function and organ preservation post cystectomy. These academic shortcomings often result in poor provider awareness and inadequate preoperative assessment. As such, it is crucial for all providers involved in female RC care to understand the necessary and available tools for preoperative evaluation, in addition to the anatomic and reconstructive techniques. This review aims to summarize the current preoperative evaluation and available tools of SF assessment and describe in detail the varying operative techniques in the preservation or restoration of SF in women after RC. The review explores the intricacies of preoperative evaluation tools, and intraoperative techniques for organ- and nerve-sparing during radical cystectomy in females. Particular emphasis on vaginal reconstruction after partial or complete resection is provided, including split-thickness skin (STF) graft vaginoplasy, pedicled flaps, myocutaneous flaps and use of bowel segments. In conclusion, this narrative review highlights the importance of understanding anatomic considerations and nerve-sparing strategies in promoting postoperative SF and quality of life. Furthermore, the review describes the advantages and limitations of each organ- and nerve-sparing technique and their impact on sexual function and overall well-being.

Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

Targeting bladder cancer: A sex sensitive perspective in mutations and outcomes.

The incidence of bladder cancer (BC) is more common in males, however, the clinical outcome for females tends to be more unfavorable, as demonstrated by a 21% increase in mortality compared to males within two years of diagnosis. While it was previously believed that the differences in outcome were solely the result of differences in sex chromosomes and hormones, it is now acknowledged that a more intricate interplay of factors is at play. By acquiring a more comprehensive understanding of these sex-specific effects, future efforts in precision medicine can be customized to an individual's biological sex. This narrative review aims to summarize our knowledge of the molecular classification of sex differences in BC by compiling the existing evidence on genetic disparities between males and females and evaluating these disparities in both noninvasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). Our findings emphasize the significance of considering sex as a factor in future clinical trials and registry studies due to established differences in immune composition, molecular profiling, and genetic mutations between males and females. Further investigation into the molecular processes involved in the evasion or resistance of immune-based therapies, such as Bacillus Calmette-Guérin and other immunotherapies, is essential to identify markers of response or resistance that vary between male and female patients. This will aid in optimizing treatment and promoting equitable outcomes, particularly in NMIBC cases.

Sequential intravesical gemcitabine-docetaxel vs. bacillus Calmette-Guerin (BCG) in the treatment of non-muscle invasive bladder cancer: A preliminary cost-effectiveness analysis.

INTRODUCTION: Treatment naïve patients with high-risk non-muscle invasive bladder cancer (NMIBC) are treated with bacillus Calmette-Guérin (BCG) therapy as the standard of care. Recently, intravesical sequential gemcitabine-docetaxel in the BCG-naïve setting was shown to be well-tolerated and effective, raising the possibility of a new first line intravesical therapy. Cost effectiveness of this intervention remains unknown; therefore, we designed a cost effectiveness study evaluating BCG vs. sequential gemcitabine-docetaxel in patients with high risk NMIBC. METHODS: Using TreeAgePro 2019 software, we developed a Markov model to evaluate BCG vs. gemcitabine-docetaxel from the U.S. Medicare perspective with a 2-year time horizon. Model probabilities and utilities were derived from published literature. Direct costs were obtained from Medicare cost databases. Our primary outcomes were effectiveness (measured in quality adjusted life years [QALYs]), cost and the incremental cost-effectiveness ratio with a willingness to pay threshold of $100,000. RESULTS: Our results indicate that while both treatments resulted in similar QALYs of 1.76, the mean costs per patient at 2 years were $12,363 and $7,090 for BCG and gemcitabine-docetaxel, respectively. Therefore, the BCG strategy was dominated by the gemcitabine-docetaxel strategy as it was equally effective and less costly. One way sensitivity analyses were completed and gemcitabine-docetaxel remained a cost-effective strategy. CONCLUSIONS: The findings of this preliminary cost-effectiveness analysis are novel in that they highlight a well tolerated, efficacious drug that is less expensive than the traditional gold standard therapy. In modern medicine, we are more often challenged by agents with marginally increased efficacy but at significantly higher costs; gemcitabine-docetaxel represents a rare entity which is a success for both patients and healthcare systems alike.

Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors.

CONTEXT: Bladder cancer (BC) is common worldwide and poses a significant public health challenge. External risk factors and the wider exposome (totality of exposure from external and internal factors) contribute significantly to the development of BC. Therefore, establishing a clear understanding of these risk factors is the key to prevention. OBJECTIVE: To perform an up-to-date systematic review of BC's epidemiology and external risk factors. EVIDENCE ACQUISITION: Two reviewers (I.J. and S.O.) performed a systematic review using PubMed and Embase in January 2022 and updated it in September 2022. The search was restricted to 4 yr since our previous review in 2018. EVIDENCE SYNTHESIS: Our search identified 5177 articles and a total of 349 full-text manuscripts. GLOBOCAN data from 2020 revealed an incidence of 573 000 new BC cases and 213 000 deaths worldwide in 2020. The 5-yr prevalence worldwide in 2020 was 1 721 000. Tobacco smoking and occupational exposures (aromatic amines and polycyclic aromatic hydrocarbons) are the most substantial risk factors. In addition, correlative evidence exists for several risk factors, including specific dietary factors, imbalanced microbiome, gene-environment risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. CONCLUSIONS: We present a contemporary overview of the epidemiology of BC and the current evidence for BC risk factors. Smoking and specific occupational exposures are the most established risk factors. There is emerging evidence for specific dietary factors, imbalanced microbiome, gene-external risk factor interactions, diesel exhaust emission exposure, and pelvic radiotherapy. Further high-quality evidence is required to confirm initial findings and further understand cancer prevention. PATIENT SUMMARY: Bladder cancer is common, and the most substantial risk factors are smoking and workplace exposure to suspected carcinogens. On-going research to identify avoidable risk factors could reduce the number of people who get bladder cancer.

Bladder and Kidney Cancer Diagnosis and Survival Increase With Medicare Eligibility at Age 65.

INTRODUCTION: Medicare eligibility at 65 has been associated with increased diagnosis and survival for certain cancers due to greater health care utilization. We aim to assess for a similar "Medicare effect" for bladder and kidney cancers, which has not been previously established. METHODS: Patients diagnosed with bladder or kidney cancer from 2000-2018 at ages 60-69 years were identified with the Surveillance, Epidemiology, and End Results database. We used age-over-age percent change calculations to characterize trends in cancer diagnoses focusing on patients aged 65. Multivariable Cox models were used to compare cancer-specific mortality across ages at diagnosis. RESULTS: We identified 63,960 patients diagnosed with bladder cancer and 52,316 diagnosed with kidney cancer. Age-over-age change in diagnosis was highest for patients aged 65 compared to all other ages for both cancers (P < .01 for both). Stratified by stage, patients aged 65 had a higher age-over-age change than those aged 61-64 or 66-69 for in situ (P = .01, P < .01, respectively), localized (P = .03, P = .01), and regional (P = .02, P = .02) bladder cancer and localized (P = .01, P = .01) kidney cancer. Bladder cancer patients aged 65 had lower cancer-specific mortality than patients aged 66 (HR = 1.17, P = .01) and 69 (HR = 1.18, P = .01), while kidney cancer patients aged 65 had lower mortality than patients aged 64 (HR = 1.18, P < .01) and 66-69. CONCLUSIONS: The age of 65, marking the onset of Medicare eligibility, is associated with more diagnoses of bladder and kidney cancer. Patients diagnosed at age 65 demonstrate decreased bladder and kidney cancer-specific mortality.

Cost-effectiveness analysis of arterial catheter insertion on robotic-assisted laparoscopic prostatectomy.

INTRODUCTION: To evaluate the utility, outcomes, and cost of arterial line placement in a single institution cohort of patients undergoing robotic-assisted laparoscopic prostatectomy (RALP). MATERIALS AND METHODS: A retrospective chart review was performed at a large tertiary care center from July 2018 through January 2021. Hospital costs and cost-effective analysis was performed on patients with and without arterial line placement. Means with standard deviations were used to report continuous variables, while numbers and percentages were utilized to describe categorical variables. T-tests and Chi-square tests compared categorical and continuous variables across study cohorts, respectively. Multivariable analyses were used to examine the association between A-line placement and outcomes as mentioned above adjusting for the effect of other co-variables. RESULTS: Among the 296 included patients, 138 (46.6%) had arterial lines. No preoperative patient characteristic predicted arterial line placement. Rates of complications and re-admissions were not statistically significant between the two groups. Arterial line use was associated with higher volumes of intraoperative fluid administration, as well as a longer hospital length of stay. Total cost and operative time did not significantly differ between cohorts, but arterial line placement increased variability of these factors. CONCLUSION: The use of arterial lines in patients undergoing RALP is not necessarily guideline-driven and does not decrease the rate of perioperative complications. However, it is associated with longer length of stay and increases variability in charge. These data show that the surgical team and anesthesia team should critically evaluate the need for arterial line placement in patients undergoing RALP.

Disparities in cause-specific mortality by race and sex among bladder cancer patients from the SEER database.

PURPOSE: Previous literature shows that more bladder cancer patients overall die from causes other than the primary malignancy. Given known disparities in bladder cancer outcomes by race and sex, we aimed to characterize differences in cause-specific mortality for bladder cancer patients by these demographics. METHODS: We identified 215,252 bladder cancer patients diagnosed with bladder cancer from 2000 to 2017 in the SEER 18 database. We calculated cumulative incidence of death from seven causes (bladder cancer, COPD, diabetes, heart disease, external, other cancer, other) to assess differences in cause-specific mortality between race and sex subgroups. We used multivariable Cox proportional hazards regression and Fine-Gray competing risk models to compare risk of bladder cancer-specific mortality between race and sex subgroups overall and stratified by cancer stage. RESULTS: 17% of patients died from bladder cancer (n = 36,923), 30% died from other causes (n = 65,076), and 53% were alive (n = 113,253). Among those who died, the most common cause of death was bladder cancer, followed by other cancer and diseases of the heart. All race-sex subgroups were more likely than white men to die from bladder cancer. Compared to white men, white women (HR: 1.20, 95% CI: 1.17-1.23) and Black women (HR: 1.57, 95% CI: 1.49-1.66) had a higher risk of dying from bladder cancer, overall and stratified by stage. CONCLUSION: Among bladder cancer patients, death from other causes especially other cancer and heart disease contributed a large proportion of mortality. We found differences in cause-specific mortality by race-sex subgroups, with Black women having a particularly high risk of dying from bladder cancer.

Global Meta-analysis of Urine Microbiome: Colonization of Polycyclic Aromatic Hydrocarbon-degrading Bacteria Among Bladder Cancer Patients.

BACKGROUND: The application of next-generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer (BC), these have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundamental questions remain how we can utilize this knowledge. OBJECTIVE: The aim of our study was to examine the disease-associated changes in urine microbiome communities globally utilizing a machine learning algorithm. DESIGN, SETTING, AND PARTICIPANTS: Raw FASTQ files were downloaded for the three published studies in urinary microbiome in BC patients, in addition to our own prospectively collected cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demultiplexing and classification were performed using the QIIME 2020.8 platform. De novo operational taxonomic units were clustered using the uCLUST algorithm and defined by 97% sequence similarity and classified at the phylum level against the Silva RNA sequence database. The metadata available from the three studies included were used to evaluate the differential abundance between BC patients and controls via a random-effect meta-analysis using the metagen R function. A machine learning analysis was performed using the SIAMCAT R package. RESULTS AND LIMITATIONS: Our study includes 129 BC urine and 60 healthy control samples across four different countries. We identified a total of 97/548 genera to be differentially abundant in the BC urine microbiome compared with that of healthy patients. Overall, while the differences in diversity metrics were clustered around the country of origin (Kruskal-Wallis, p < 0.001), collection methodology was a driver of microbiome composition. When assessing dataset from China, Hungary, and Croatia, data demonstrated no discrimination capacity to distinguish between BC patients and healthy adults (area under the curve [AUC] 0.577). However, inclusion of samples with catheterized urine improved the diagnostic accuracy of prediction for BC to AUC 0.995, with precision-recall AUC = 0.994. Through elimination of contaminants associated with the collection methodology among all cohorts, our study identified increased abundance of polycyclic aromatic hydrocarbon (PAH)-degrading bacteria Sphingomonas, Acinetobacter, Micrococcus, Pseudomonas, and Ralstonia to be consistently present in BC patients. CONCLUSIONS: The microbiota of the BC population may be a reflection of PAH exposure from smoking, environmental pollutants, and ingestion. Presence of PAHs in the urine of BC patients may allow for a unique metabolic niche and provide necessary metabolic resources where other bacteria are not able to flourish. Furthermore, we found that while compositional differences are associated with geography more than with disease, many are driven by the collection methodology. PATIENT SUMMARY: The goal of our study was to compare the urine microbiome of bladder cancer patients with that of healthy controls and evaluate any potential bacteria that may be more likely to be found in patients with bladder cancer. Our study is unique as it evaluates this across multiple countries, to find a common pattern. After we removed some of the contamination, we were able to localize several key bacteria that are more likely to be found in the urine of bladder cancer patients. These bacteria all share their ability to break down tobacco carcinogens.